Eplerenone inhibits aldosterone-induced renal expression of cyclooxygenase
Introduction: The upregulation of cyclooxygenase (COX) expression by aldosterone (ALDO) or high salt diet intake is very interesting and complex in the light of what is known about the role of COX in renal function. Thus, in this study, we hypothesize that apocynin (APC) and/or eplerenone (EPL) inhi...
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doaj-d13ed5f2c2db4708a80a3b5fa27222fe2021-05-02T14:45:29ZengHindawi - SAGE PublishingJournal of the Renin-Angiotensin-Aldosterone System1470-32031752-89762012-09-011310.1177/1470320312443911Eplerenone inhibits aldosterone-induced renal expression of cyclooxygenaseMA Bayorh0A Rollins-Hairston1J Adiyiah2D Lyn3D Eatman4Department of Pharmacology/Toxicology, Morehouse School of Medicine, USADepartment of Pharmacology/Toxicology, Morehouse School of Medicine, USADepartment of Pharmacology/Toxicology, Morehouse School of Medicine, USADepartment of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, USADepartment of Pharmacology/Toxicology, Morehouse School of Medicine, USAIntroduction: The upregulation of cyclooxygenase (COX) expression by aldosterone (ALDO) or high salt diet intake is very interesting and complex in the light of what is known about the role of COX in renal function. Thus, in this study, we hypothesize that apocynin (APC) and/or eplerenone (EPL) inhibit ALDO/salt-induced kidney damage by preventing the production of prostaglandin E 2 (PGE 2 ). Methods: Dahl salt-sensitive rats on either a low-salt or high-salt diet were treated with ALDO (0.2 mg pellet) in the presence of EPL (100 mg/kg/day) or APC (1.5 mM). Indirect blood pressure, prostaglandins and ALDO levels and histological changes were measured. Results: Cyclooxygenase-2 (COX-2) levels were upregulated in the renal tubules and peritubular vessels after high-salt intake, and APC attenuated renal tubular COX-2 protein expression induced by ALDO. Plasma PGE 2 levels were significantly reduced by ALDO in the rats fed a low-salt diet when compared to rats fed a high-salt diet. PGE 2 was blocked by EPL but increased in the presence of APC. Conclusions: The beneficial effects of EPL may be associated with an inhibition of PGE 2 . The mechanism underlying the protective effects of EPL is clearly distinct from that of APC and suggests that these agents can have differential roles in cardiovascular disease.https://doi.org/10.1177/1470320312443911 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
MA Bayorh A Rollins-Hairston J Adiyiah D Lyn D Eatman |
spellingShingle |
MA Bayorh A Rollins-Hairston J Adiyiah D Lyn D Eatman Eplerenone inhibits aldosterone-induced renal expression of cyclooxygenase Journal of the Renin-Angiotensin-Aldosterone System |
author_facet |
MA Bayorh A Rollins-Hairston J Adiyiah D Lyn D Eatman |
author_sort |
MA Bayorh |
title |
Eplerenone inhibits aldosterone-induced renal expression of cyclooxygenase |
title_short |
Eplerenone inhibits aldosterone-induced renal expression of cyclooxygenase |
title_full |
Eplerenone inhibits aldosterone-induced renal expression of cyclooxygenase |
title_fullStr |
Eplerenone inhibits aldosterone-induced renal expression of cyclooxygenase |
title_full_unstemmed |
Eplerenone inhibits aldosterone-induced renal expression of cyclooxygenase |
title_sort |
eplerenone inhibits aldosterone-induced renal expression of cyclooxygenase |
publisher |
Hindawi - SAGE Publishing |
series |
Journal of the Renin-Angiotensin-Aldosterone System |
issn |
1470-3203 1752-8976 |
publishDate |
2012-09-01 |
description |
Introduction: The upregulation of cyclooxygenase (COX) expression by aldosterone (ALDO) or high salt diet intake is very interesting and complex in the light of what is known about the role of COX in renal function. Thus, in this study, we hypothesize that apocynin (APC) and/or eplerenone (EPL) inhibit ALDO/salt-induced kidney damage by preventing the production of prostaglandin E 2 (PGE 2 ). Methods: Dahl salt-sensitive rats on either a low-salt or high-salt diet were treated with ALDO (0.2 mg pellet) in the presence of EPL (100 mg/kg/day) or APC (1.5 mM). Indirect blood pressure, prostaglandins and ALDO levels and histological changes were measured. Results: Cyclooxygenase-2 (COX-2) levels were upregulated in the renal tubules and peritubular vessels after high-salt intake, and APC attenuated renal tubular COX-2 protein expression induced by ALDO. Plasma PGE 2 levels were significantly reduced by ALDO in the rats fed a low-salt diet when compared to rats fed a high-salt diet. PGE 2 was blocked by EPL but increased in the presence of APC. Conclusions: The beneficial effects of EPL may be associated with an inhibition of PGE 2 . The mechanism underlying the protective effects of EPL is clearly distinct from that of APC and suggests that these agents can have differential roles in cardiovascular disease. |
url |
https://doi.org/10.1177/1470320312443911 |
work_keys_str_mv |
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